| Project/Area Number |
03670509
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Jikei Univ.School of Medicine |
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Principal Investigator |
TOKORO Toshoharu Jikei Univ.Pediatr. Lecture, 医学部, 講師 (40112841)
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| Co-Investigator(Kenkyū-buntansha) |
IDA H Jikei Univ.Pediatr. intructor, 医学部, 助手 (90167255)
SASAKI N Jikei Univ.Pediatr. intructor, 医学部, 助手 (50170684)
ITO F Jikei Univ.Pediatr. assistant of professo, 医学部, 助教授 (10057010)
ETO Y Jikei Univ.Pediatr. assistant of professo, 医学部, 助教授 (50056909)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Niemann-Pick Disease / Cholesterol esterification / Genetic homogenity / Cross hybridization / SPM mouse / CDS mouse / スフィンゴシェリン / NemannーPick病 / コレステロ-ル / コレステロ-ルエステル / 細胞内転送機構 / 胎児肝細胞移植 |
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| Research Abstract |
The similarity of biological and morphorogical findings between BALB/c CSD and C57BL/KsJ SPM mice, both of them are suspected to be a mouse model of Niemann-Pick disease type A or C, prompted us to examine the genetic analysis for these mice models. Crosshybridization studies between the heterozygote of CSD mise and SPM mice were done. Forty-two offsprings(SCH) were used for this analysis. Bichemical analysis showed that several lipids, cholesterol, sphingomyelin, GM_2-ganglioside and GM_3 - ganglioside, were accumulated in SCH mice organs comparable to SPM and CSD mice organs, Esterification of exogenously administered cholesterol in fibroblasts showed a level of deficiency comparable to the levels in SPM and CSD mice. Lysosomal hydrolase activity in SCH mice liver was elevated to a level midway between the values measured in SPM and CSD mice tissue. Sphingomyelinase activity in fibroblasts was reduced to the same extent in SCH organs as in SPM and CSD mice organs. In the morphological studies, myeiln figures were observed in liver, spleen and brain tissues by electromicroscopy. 25% of F_1 mice showed such abnormal findings in the biochemical and morphological analysis. These results indicate that the locarization of the mutation in these SPM mice can be used as a model for human Niemann-Pick disease type C.
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